Macrolides induce severe cardiotoxicity and developmental toxicity in zebrafish embryos

Area of Science:

• Environmental Toxicology
• Aquatic Pharmacology
• Developmental Biology

Background:

• Macrolide antibiotics (MALs) are extensively used in human and animal health.
• MALs and their metabolites contaminate aquatic environments, posing ecological risks.
• While MALs' cardiotoxicity in mammals is known, their impact on aquatic organisms is unclear.

Purpose of the Study:

• To assess the cardiotoxicity and developmental toxicity of four common MALs in zebrafish embryos.
• To investigate the mechanisms of toxicity, including oxidative stress and apoptosis.

Main Methods:

• Zebrafish embryos were exposed to azithromycin, clarithromycin, tilmicosin (TMS), and tylosin.
• Heart rate was monitored at 2 days post-fertilization.
• Acute and developmental toxicity of TMS were evaluated at 4 days post-fertilization.
• Oxidative stress markers (SOD, MDA) and apoptosis-related gene/protein expression (p53, bcl 2, bax, caspase 3, caspase 9) were analyzed.

Main Results:

• A biphasic effect on heart rate was observed: increased at low MAL concentrations and decreased at high concentrations.
• TMS exposure led to pericardial edema and spinal curvature in zebrafish embryos.
• TMS induced oxidative stress, evidenced by decreased SOD activity and increased MDA levels.
• TMS triggered apoptosis in zebrafish embryos, confirmed by upregulated apoptosis-related genes and proteins.

Conclusions:

• Macrolide antibiotics exhibit significant cardiotoxicity and developmental toxicity in zebrafish embryos.
• Oxidative stress and apoptosis are key mechanisms underlying MAL-induced toxicity.
• The widespread use of MALs, particularly in aquaculture, warrants caution due to potential adverse effects on aquatic ecosystems.